Synthesis of 99mTc-labeled 2-Mercaptobenzimidazole as a novel radiotracer to diagnose tumor hypoxia

Syed Faheem Askari Rizvi; Haixia Zhang; Sajid Mehmood; Mahmoud Sanad

doi:10.1016/j.tranon.2020.100854

Synthesis of ^99mTc-labeled 2-Mercaptobenzimidazole as a novel radiotracer to diagnose tumor hypoxia

Transl Oncol. 2020 Dec;13(12):100854. doi: 10.1016/j.tranon.2020.100854. Epub 2020 Aug 28.

Authors

Syed Faheem Askari Rizvi¹, Haixia Zhang², Sajid Mehmood³, Mahmoud Sanad⁴

Affiliations

¹ College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, Gansu, PR China; Isotope Production Group, Chemistry Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), P.O. Nilore, Islamabad, Punjab, Pakistan.
² College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, Gansu, PR China. Electronic address: Zhanghx@lzu.edu.cn.
³ Isotope Production Group, Chemistry Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), P.O. Nilore, Islamabad, Punjab, Pakistan.
⁴ Labeled Compounds Department, Hot Laboratories Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.

Abstract

Discovery of ^99mTc-labeled imidazole derivatives as a potential radiotracer for hypoxic tumor imaging is considered to be of great interest because of non-invasive detection capabilities. 2-Mercaptobenzimidazole (2-MBI) was successfully synthesized, characterized and radiolabeled with [^99mTc (CO)₃(H₂O)₃]⁺ intermediate to form ^99mTc-2-MBI complex with radiochemical purity of ≥95% yield as observed by instant-thin layer chromatography (ITLC) and radio-high performance liquid chromatography (radio-HPLC). The ^99mTc-2-MBI complex was observed to be stable in saline and serum with no noticeable decomposition at room temperature and 37 °C, respectively, over a time period of 24 h. Biodistribution results in Balb/c mice bearing S180 tumor show that ^99mTc-2-MBI highly internalized in tumor tissue, also possess preferably high tumor/muscle and tumor/blood ratios 4.14 ± 0.77 and 3.91 ± 0.63, respectively at 24 h incubation. Scintigraphic imaging study shows ^99mTc-2-MBI is visibly accumulated in hypoxic tumor tissue, suggesting it would be a promising radiotracer for early stage diagnosis of tumor hypoxia.

Keywords: (99m)Tc-2-MBI; Imidazole; Radiotracer; S180 Tumor; Scintigraphy study; Tumor hypoxia.